Frail old patients as a target population for cancer trials

The recent distinction between co-morbidity and multi-morbidity well stresses the difficulty of managing old patients with cancer whose complexity is not captured by a list of diagnoses or biological burden alone. The most adequate answer found by oncologists and geriatricians was to work together for better evaluating the physiological age and body reserve of the patient. The gold standard tool to assess old patient with cancer is named Comprehensive Geriatric Assessment. Its systematic application needs geriatric competences and time. In this context, a great number of cancer patients are considered as "frail” because they have reduced available physiological reserves. They might not withstand stress when challenged. Oncologists and geriatricians have imagined an innovative process to change the screening procedure of these patients, determine the prognosis, adapt the treatment strategy, to increase the patient's survival and his/her quality of life. The internet website "www.clinicaltrials.com” only lists 8 studies focused on frail elders with cancer. Six of them are focused on specific cancers or specific treatments, one was applied to all kind of cancers and the last was an opinion overview from oncologists and geriatricians. The selection criteria of frail patients are very diverse and probably include cancer patients who are not comparable. It is now time to try to identify new practical, reliable and accurate tools to facilitate the inclusion of the same kind of patients suffering from the same kind of cancer to be able to give more appropriate care and at the same time to constitute a valuable data base. Existing tools are reviewed and analyze

High dose melphalan, BCNU and etoposide with autologous bone marrow transplantation for Hodgkin's disease.

Thirty-eight patients with previously treated Hodgkin's disease were given high dose combination chemotherapy using melphalan and BCNU and autologous bone marrow transplantation. In 25 patients etoposide was added in conventional dosage. During the course of the study the dose of melphalan was increased from 80 to 140 mg m-2 and the dose of BCNU from 300 to 600 mg m-2. The response rate was 76% with 53% complete remission. Forty-five per cent of the patients are free of disease at 4-20 months follow-up. There were eight (26%) treatment-related deaths due to lung damage (seven cases) and irreversible cardiac failure (one case). Fatal lung damage occurred only in patients receiving 600 mg m-2 of BCNU with high dose melphalan. The dose of BCNU given with high dose melphalan should not exceed 500 mg m-2. This treatment is effective against relapsed Hodgkin's disease but must be used cautiously. The best time for its use remains to be determined

Urban Ecosystem accounts following the SEEA EA standard: A pilot application in Europe

National and local authorities are promoting restoration actions in urban areas to mitigate societal challenges such as urban heat island, poor air quality or biodiversity loss. Urban re-greening is among the implementation actions supporting targets of the European Green Deal, EU Biodiversity Strategy 2030, its proposal for a Nature Restoration Law, and the proposal for an amendment of the Regulation on Environmental Accounts. However, to monitor progress towards policy targets and an overall enhancement of urban ecosystems, policy makers require regular, consistent and comparable data. The implementation of United Nation's System of Environmental Economic Accounting - Ecosystem Accounting (SEEA EA) on urban ecosystems could help to track changes in their ecosystem extent, condition, services and derived benefits. Despite SEEA EA became a statistical standard, it has been only tested in pilot exercises, of which very few are urban ecosystem accounts. This report presents a pilot SEEA EA urban ecosystem account for EU-27 and EFTA Member States in 2018. It discusses challenges for the development of urban ecosystem accounts and potential solutions. The outputs illustrate where re-greening efforts should be applied and discusses feasibility and potential issues of targets. The report also presents key insights to operationalise SEEA EA for urban ecosystem accounts. It provides an instructive guiding example to national and local authorities starting to draft their own urban ecosystem accounts

Disease activity states, reasons for discontinuation and adverse events in 1038 Italian children with juvenile idiopathic arthritis treated with etanercept

The advent of biologic medications has increased considerably the potential for treatment benefit in juvenile idiopathic arthritis (JIA), with clinical remission being now achievable in a substantial proportion of patients. However, there is a need of data from the real world of clinical practice to evaluate thoroughly the efficacy and safety profile of the biologic agents currently approved

Reduced dose of subcutaneous cladribine induces identical response rates but decreased toxicity in pretreated chronic lymphocytic leukaemia

Purpose To study the efficacy and the safety of cladribine (2-chlorodeoxyadenosine, 2-CDA) administered as 24-hour infusions or as subcutaneous bolus injections at two different doses to patients with relapsing or refractory chronic lymphocytic leukaemia (CLL). Patients and methods In this non randomised 2-cohort study, 20 patients with pretreated CLL received cladribine at a dose of 0.7 mg/kg/cycle as continuous i.v. infusions over seven days (group 1) and 35 patients were treated at a reduced dose of 0.5 mg/kg/cycle given as s.c. bolus injections for five days (group 2). After two cycles of four week duration, response was assessed. In the case of progressive disease, therapy was discontinued, otherwise a maximum of four additional cycles were administered until best response. Results A total of 130 cycles were administered (group 1: 41, group 2: 89). Patient characteristics in both groups were comparable. The median dose intensities were 0.172 mg/kg per week and 0.123 mg/kg per week for groups 1 and 2, respectively (P ≤ 0.0001). The overall response rate for all 55 patients was 38% (95% confidence interval (95% CI): 25%-52%), with 5% CR and 33% PR. Response was similar in both patient groups (35% in group 1, 40% in group 2). No association between cladribine dose intensity and response rate was found, and there was no difference between patients relapsing after or refractory to previous therapies (11 of 24 vs. 10 of 31). Median remission duration was six months in both groups. Toxicity, in particular infections (all WHO grades, 34% in group 1 versus 7% in group 2) and myelosuppression (grade 1-4 neutropenia, 72% versus 41% of cladribine cycles) were statistically significantly more frequent in group 1. Conclusion Cladribine is active in heavily pretreated patients with chronic lymphocytic leukaemias. Dose reduction by 29% led to similar response and remission duration, but to a significant decrease of myelotoxicity and risk of infection. Cladribine administered as s.c. bolus injections at 0.5 mg/kg per cycle is safe and this dose level should not be exceeded in this patient populatio

Irreversible Aging Dynamics and Generic Phase Behavior of Aqueous Suspensions of Laponite

In this work we study the aging behavior of aqueous suspension of Laponite having 2.8 weight % concentration using rheological tools. At various salt concentration all the samples demonstrate orientational order when observed using crossed polarizers. In rheological experiments we observe inherent irreversibility in the aging dynamics which forces the system not to rejuvenate to the same state in the shear melting experiment carried out at a later date since preparation. The extensive rheological experiments carried out as a function of time elapsed since preparation demonstrate the self similar trend in the aging behavior irrespective of the concentration of salt. We observe that the exploration of the low energy states as a function of aging time is only kinetically affected by the presence of salt. We estimate that the energy barrier to attain the low energy states decreases linearly with increase in the concentration of salt. The observed superposition of all the elapsed time and the salt concentration dependent data suggests that the aging that occurs in low salt concentration systems over a very long period is qualitatively similar to the aging behavior observed in systems with high salt concentration over a shorter period.Comment: 27 pages, 8 figures. Langmuir, in pres